Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension

Lincevicius, Gisele S.; Shimoura, Caroline Gusson; Nishi, Érika E.; Perry, Juliana C.; Casarini, Dulce Elena; Gomes, Guiomar Nascimento; Bergamaschi, Cássia T.; Campos, Rui

doi:10.1093/ajh/hpu300

Cited by 25 publications

(19 citation statements)

References 40 publications

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“…The increased sympathetic tone seen in renovascular hypertension has also recently been linked to an up‐regulation of AT 1 R in the rostroventrolateral medulla (Lincevicius et al . ). Thus, it is possible that brainstem inflammation and sympathetic overactivity in renovascular hypertension may be driven by elevated ANG II signalling.…”

Section: Discussionmentioning

confidence: 97%

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Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats

Pijacka

McBryde

Marvar

et al. 2016

The Journal of Physiology

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The peripheral chemoreflex is known to be hyper-responsive in both spontaneously hypertensive (SHR) and Goldblatt hypertensive (two kidney one clip; 2K1C) rats. We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and reveal the potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, and then underwent CSD (n = 9) or sham CSD (n = 9) 5 weeks after renal artery clipping, in comparison with normal Wistar rats (n = 5). After 21 days, renal function was assessed, and tissue was collected to assess sympathetic postganglionic intracellular calcium transients ([Ca ] ) and immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in ABP (Wistar: 98 ± 4 mmHg vs. 2K1C: 147 ± 8 mmHg; P < 0.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuroinflammatory markers and enhanced [Ca ] in stellate neurons (P < 0.05). CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase in ABP seen in 2K1C+sham CSD rats, with a between-group difference of 14 ± 2 mmHg by week 3 (P < 0.01), which was accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho-vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca ] evoked responses from stellate neurons, and also reduced indicators of brainstem inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and improves renal function. This may be mediated by improvements in autonomic balance, functional remodelling of post-ganglionic neurons and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.

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Section: Discussionmentioning

confidence: 97%

“…; Lincevicius et al . ). Values of matching systolic blood pressure (SBP) variations with reflex heart rate (HR) responses were plotted separately for each vasoactive drug to create linear regression curves for each group, and their slopes were compared to evaluate changes in baroreflex sensitivity (beats min –1 mmHg –1 ).…”

Section: Methodsmentioning

confidence: 97%

Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats

Pijacka

McBryde

Marvar

et al. 2016

The Journal of Physiology

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“…; Lincevicius et al . ). Animals were then randomly divided into two groups – Time Control and Carotid Body Resection (CBR).…”

Section: Methodsmentioning

confidence: 97%

Variable role of carotid bodies in cardiovascular responses to exercise, hypoxia and hypercapnia in spontaneously hypertensive rats

Pijacka

Katayama

Salgado

et al. 2018

The Journal of Physiology

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The carotid body has recently emerged as a promising therapeutic target for treating cardiovascular disease, but the potential impact of carotid body removal on the dynamic cardiovascular responses to acute stressors such as exercise, hypoxia and hypercapnia in hypertension is an important safety consideration that has not been studied. We first validated a novel surgical approach to selectively resect the carotid bodies bilaterally (CBR) sparing the carotid sinus baroreflex. Second, we evaluated the impact of CBR on the cardiovascular responses to exercise, hypoxia and hypercapnia in conscious, chronically instrumented spontaneously hypertensive (SH) rats. The results confirm that our CBR technique successfully and selectively abolished the chemoreflex, whilst preserving carotid baroreflex function. CBR produced a sustained fall in arterial pressure in the SH rat of ∼20 mmHg that persisted across both dark and light phases (P < 0.001), with baroreflex function curves resetting around lower arterial pressure levels. The cardiovascular and respiratory responses to moderate forced exercise were similar between CBR and Sham rats. In contrast, CBR abolished the pressor response to hypoxia seen in Sham animals, although the increases in heart rate and respiration were similar between Sham and CBR groups. Both the pressor and the respiratory responses to 7% hypercapnia were augmented after CBR (P < 0.05) compared to sham. Our finding that the carotid bodies play a critical role in maintaining arterial pressure during hypoxia has important implications when considering resection therapy of the carotid body in disease states such as hypertension as well as heart failure with sleep apnoea.

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“…However, no study investigated if aldosterone acting in the hindbrain changes arterial pressure, particularly at the dose that it produces sodium appetite. Studies showing that the MR antagonist spironolactone increased baroreceptor reflex sensitivity in a renovascular hypertension model or that injection of the MR antagonist eplerenone into the NTS increased baroreflex sensitivity in salt-loaded rats suggest that endogenous aldosterone or corticosterone may be involved in the control of baroreflex function (Lincevicius et al, 2015;Masuda et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes

et al. 2018

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Aldosterone infusion into the 4th ventricle (4th V), upstream the nucleus of the solitary tract (NTS), produces strong 0.3 M NaCl intake. In the present study, we investigated whether aldosterone infusion into the 4th V activates HSD2 neurons, changes renal excretion, or alters blood pressure and cardiovascular reflexes. Chronic infusion of aldosterone (100 ng/h) into the 4th V increased daily 0.3 M NaCl intake (up to 44 ± 10, vs. vehicle: 5.6 ± 3.4 ml/24 h) and also c-Fos expression in HSD2 neurons in the NTS and in non-HSD2 neurons in the NTS. Natriuresis, diuresis and positive sodium balance were present in rats that ingested 0.3 M NaCl, however, renal excretion was not modified by 4th V aldosterone in rats that had no access to NaCl. 4th V aldosterone also reduced baroreflex sensitivity (-2.8 ± 0.5, vs. vehicle: -5.1 ± 0.9 bpm/mmHg) in animals that had sodium available, without changing blood pressure. The results suggest that sodium intake induced by aldosterone infused into the 4th V is associated with activation of NTS neurons, among them the HSD2 neurons. Aldosterone infused into the 4th V in association with sodium intake also impairs baroreflex sensitivity, without changing arterial pressure.

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Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension

Abstract: Aldosterone contributes to autonomic dysfunction and intrarenal injury in 2K1C, these effects are mediated by the CNS.

Cited by 25 publications

References 40 publications

Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats

Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats

Variable role of carotid bodies in cardiovascular responses to exercise, hypoxia and hypercapnia in spontaneously hypertensive rats

Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes

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